Leuprorelin (Leuprolide)

What is leuprorelin?

Leuprorelin (the INN; called leuprolide in the United States) is a synthetic analogue of gonadotropin-releasing hormone (GnRH). It is a regulator-approved prescription medicine, first approved by the FDA in 1985, and is given as an injection or long-acting depot. It belongs to the same class as triptorelin, goserelin and buserelin.

Identity

Leuprorelin is not the same as gonadorelin (native GnRH, which stimulates the axis when given in pulses), GnRH antagonists such as degarelix, relugolix or cetrorelix (which suppress without a flare), or kisspeptin, which acts upstream of GnRH.

How it works

Continuous exposure to a GnRH agonist first stimulates the pituitary, causing a temporary rise in LH, FSH and sex hormones (the "flare"). The pituitary then becomes desensitised, and sex hormones fall to castrate levels. That suppression is the therapeutic goal in hormone-sensitive conditions, and also the source of most adverse effects.

Approved uses and evidence

• Advanced prostate cancer: in a randomised trial of 199 men with metastatic prostate cancer, leuprolide suppressed testosterone as well as diethylstilbestrol, with objective responses of 86% versus 85%; diethylstilbestrol caused more gynaecomastia, nausea, oedema and thromboembolism, and leuprolide more hot flushes (Leuprolide Study Group 1984). Eligard and Camcevi are depot formulations for the same indication (Perez-Marreno 2002; labels).
• Endometriosis: a placebo-controlled trial (n=52) showed significant reductions in dysmenorrhoea, pelvic pain and tenderness (Dlugi 1990). In a 12-month trial (n=201), women without add-back therapy lost 6.3% of bone density, while norethindrone-acetate-based add-back preserved it (Hornstein 1998). The label allows use alone or with norethindrone acetate add-back.
• Uterine fibroids: approved together with iron for preoperative haematological improvement (label).
• Central precocious puberty: Lupron Depot-PED and Fensolvi are approved; randomised and phase 3 trials studied 3-month and 6-month depots (Lee 2012; Klein 2023).

HERO: leuprolide versus relugolix

In the phase 3 HERO trial in advanced prostate cancer (Shore 2020; NCT03085095), oral relugolix (n=622) was compared with leuprolide (n=308). Sustained castration was achieved in 96.7% with relugolix versus 88.8% with leuprolide. No leuprolide patient was at castrate level on day 4, reflecting the agonist flare and slower onset. Major adverse cardiovascular events occurred in 6.2% with leuprolide versus 2.9% with relugolix (hazard ratio 0.46). The trial was sponsored by the maker of relugolix.

Warnings and precautions

Current FDA labels for leuprolide products carry no boxed warning. The main risks are listed under Warnings and Precautions:

• Initial flare: a temporary rise in testosterone or other sex hormones at the start of treatment (the Lupron Depot label describes roughly a 50% increase above baseline in men), which can transiently worsen symptoms.
• Hyperglycaemia/diabetes and cardiovascular risk in men: in October 2010 the FDA required GnRH-agonist labels to add warnings about diabetes, heart attack, sudden cardiac death and stroke in men treated for prostate cancer. In a Medicare cohort of 73,196 men, GnRH-agonist use was associated with diabetes (adjusted HR 1.44), coronary heart disease (HR 1.16), myocardial infarction (HR 1.11) and sudden cardiac death (HR 1.16) (Keating 2006). These are observational associations; causality has not been established.
• Bone loss: loss of bone mineral density, which may be only partly reversible (label; Hornstein 1998). In a SEER-Medicare cohort of 50,613 men, fractures occurred in 19.4% with androgen deprivation versus 12.6% without (Shahinian 2005).
• QT prolongation: androgen deprivation can prolong the QT interval (labels).
• Labels also list convulsions, severe cutaneous adverse reactions, psychiatric events and pseudotumor cerebri in children, and embryo-fetal toxicity.

Off-label claims and misuse

• Autism ("Lupron protocol"): an uncontrolled report on 11 children, promoted with chelation, is an example of misuse rather than evidence. The physician behind it had his Maryland medical licence suspended in 2011 and revoked in 2012, partly over this treatment.
• Alzheimer's disease: leuprolide has been investigated (for example, the LUCINDA study design) but is not approved for it.
• "PCT" or performance: forum and vendor claims that leuprolide aids testosterone recovery or performance are unsupported. In men, the initial flare is why it is prohibited in sport.

Grey-market "research leuprolide" has not been analytically studied; approved products are the reference point.

Sport

The 2026 WADA Prohibited List names leuprorelin under S2.2.1, testosterone-stimulating peptides in males ("GnRH … and its agonist analogues"). It is prohibited at all times for male athletes.

Dosing

No dose is given here. Doses, intervals and formulations depend on the product and indication and are defined only by the official prescribing information — see the Lupron Depot FDA label on DailyMed (opens in a new tab) and the other labels in the references.

Claims vs evidence

Related pages

Gonadorelin, Triptorelin, Goserelin, Buserelin, Kisspeptin.